Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. Here, ...we hypothesized that cyanidin 3-glucoside (C3G), a typical anthocyanin reported to possess potent anti-inflammatory properties, would ameliorate obesity-associated inflammation and metabolic disorders, such as insulin resistance and hepatic steatosis in mouse models of diabesity. Male C57BL/6J obese mice fed a high-fat diet for 12 weeks and genetically diabetic db/db mice at an age of 6 weeks received dietary C3G supplementation (0.2%) for 5 weeks. We found that dietary C3G lowered fasting glucose levels and markedly improved the insulin sensitivity in both high-fat diet fed and db/db mice as compared with unsupplemented controls. White adipose tissue messenger RNA levels and serum concentrations of inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1) were reduced by C3G, as did macrophage infiltration in adipose tissue. Concomitantly, hepatic triglyceride content and steatosis were alleviated by C3G. Moreover, C3G treatment decreased c-Jun N-terminal kinase activation and promoted phosphorylation and nuclear exclusion of forkhead box O1 after refeeding. These findings clearly indicate that C3G has significant potency in antidiabetic effects by modulating the c-Jun N-terminal kinase/forkhead box O1 signaling pathway and the related inflammatory adipocytokines.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and it is characterized by a series of fatty liver diseases that can lead to severe liver disease. Although ...no therapeutic drug has been approved as an effective therapy for NAFLD to date, dietary changes and physical activity are thought to be the cornerstone of NAFLD management. For this reason, some articles are available to analyze the studies done so far using various modifications of intermittent fasting (IF) among animals and patients with NAFLD. Data from preclinical and clinical trials suggested that IF positively impacts inflammatory and metabolic markers in both animals and humans. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. IF has been shown to have positive benefits in alleviating metabolic disorders, promoting the browning of white tissue, resetting circadian rhythm, and activating autophagy of cells. This review is intended to provide a detailed synopsis of the protocols, potential mechanisms of action, and supporting evidence for IF in NAFLD. We will highlight what is currently known about IF approaches in NAFLD treatments in clinical populations with mechanism insight from animal studies, and the safety concerns in certain patient groups.
Graphical Abstract
The protocols of intermittent fasting (IF) are various. Data from trials suggested that IF positively impacts both humans and animals. IF has been shown to have potential treatments for nonalcoholic fatty liver disease.
Arsenic can cause neurodegenerative diseases of the brain, but the definite mechanism is still unknown. In this study, to discuss the disturbances on brain metabolome and lipidome under subchronic ...arsenic exposure, we treated mice with the arsenic-containing feed (concentration of total arsenic = 30 mg/kg) prepared in accordance with the proportion of rice arsenicals for 16 weeks and performed metabolomics and lipidomics studies respectively using UHPLC-Triple-TOF-MS/MS and UHPLC-Q Exactive Focus MS/MS on mice brain. In addition, the distributions of arsenical metabolites along the feed-gut-blood-brain chain were analyzed by ICP-MS and HPLC-ICP-MS, and fecal microbial variations were investigated by 16 s sequencing. The data showed that although only a tiny amount of arsenic (DMA=0.101 mg/kg, uAs=0.071 mg/kg) enters the brain through the blood-brain barrier, there were significant changes in brain metabolism, including 118 metabolites and 17 lipids. These different metabolites were involved in 30 distinct pathways, including glycometabolism, and metabolisms of lipid, nucleic acid, and amino acid were previously reported to be correlated with neurodegenerative diseases. Additionally, these different metabolites were significantly correlated with 12 gut bacterial OTUs, among which Lachnospiraceae, Muribaculaceae, Ruminococcaceae, and Erysipelotrichaceae were also previously reported to be related to the distortion of metabolism, indicating that the disturbance of metabolism in the brain may be associated with the disturbance of gut microbes induced by arsenic. Thus, the current study demonstrated that the brain metabolome and lipidome were significantly disturbed under subchronic arsenic exposure, and the disturbances also significantly correlated with some gut microbiome and may be associated with neurodegenerative diseases. Although preliminary, the results shed some light on the pathophysiology of arsenic-caused neurodegenerative diseases.
•Significant arsenic accumulation was observed in brain tissue after exposure to arsenic in mice food for 16 weeks.•Arsenic exposure would disturb metabolic spectrum and pathway in the brain, thereby affecting neurodegenerative diseases.•The correlation between the differential metabolites and the gut bacterial may be related to the distortion of metabolism.
Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the ...main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.
Polyphenols, including anthocyanins, from various plant foods are effective in reducing the severity of atherosclerosis in animal and human studies. Due to the poor understanding of the ...bioavailability of anthocyanins, the potential antiatherogenic mechanisms underlying the action remain largely unknown. Herein, we found that oral gavage of cyanidin-3-O-β-glucoside (Cy-3-G) could be transformed into protocatechuic acid (PCA), and the plasma maximal levels of Cy-3-G were 3.7-fold lower than that of PCA in the apolipoprotein E (ApoE)-deficient mice. Subsequently, we observed that PCA treatment has a higher capacity than Cy-3-G treatment in decreasing CC chemokine receptor 2 (CCR2) expression in the mouse peripheral blood monocytes (PBMs), along with reducing the mouse PBMs chemokine toward CC ligand-2 (CCL2) in a Boyden chamber. Interesting, in the ApoE-deficient mouse model, orally gavaged with Cy-3-G has a higher ability than gavaged with PCA to reduce CCR2 expression in PBMs. PBMs deprived from the Cy-3-G-treated ApoE-deficient mice have a lower ability than those from PCA-treated animals to migrate toward CCL2. Furthermore, as compared with the PCA group, Cy-3-G treatment more efficiently reduced thioglycollate-induced macrophage infiltration into the abdominal cavity. Thus, we suggest that Cy-3-G may reduce the monocyte infiltration in mice via down-regulation of CCR2 expression in monocytes, at least in part, with the aid of its metabolite PCA. These above data imply that the anti-monocyte/macrophage infiltration property of Cy-3-G and its metabolite PCA may be an important antiatherogenic mechanism for anthocyanins.
Mangiferin is the main bioactive component in mango leaves, which possesses anti‐inflammatory, antioxidative, antidiabetic, immunomodulatory, and antitumor activities. In the present study, a ...microwave‐assisted extraction method was developed for the extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid‐to‐solid ratio, microwave power, and extraction time were optimized by single‐factor experiments and response surface methodology. The optimal extraction conditions were 45% ethanol, liquid‐to‐solid ratio of 30:1 (mL/g), and extraction time of 123 s under microwave irradiation of 474 W. Under optimal conditions, the yield of mangiferin was 36.10 ± 0.72 mg/g, significantly higher than that of conventional extraction. The results obtained are beneficial for the full utilization of mango leaves and also indicate that microwave‐assisted extraction is a very useful method for extracting mangiferin from plant materials.
: Anthocyanins are naturally occurring compounds that impart color to fruits, vegetables, and plants. This study aims to optimize the microwave‐assisted extraction (MAE) conditions of anthocyanins ...from mulberry (M. atropurpurea Roxb.) using response surface methodology (RSM). A Box–Behnken experiment was employed in this regard. Methanol concentration, microwave power, and extraction time were chosen as independent variables. The optimized conditions of MAE were as follows: 59.6% acidified methanol, 425 W power, 25 (v/w) liquid‐to‐solid ratio, and 132 s time. Under these conditions, 54.72 mg anthocyanins were obtained from 1.0 g mulberry powder. Furthermore, 8 anthocyanins were identified by high‐performance liquid chromatography‐electrospray ionization‐mass spectrometry (HPLC‐ESI‐MS) in mulberry extract. The results showed that cyanidin‐3‐glucoside and cyanidin‐3‐rutinoside are the major anthocyanins in mulberry. In addition, in comparison with conventional extraction, MAE is more rapid and efficient for extracting anthocyanins from mulberry.
Background:
Recently, many studies have demonstrated that long non-coding RNAs (lncRNAs) are abnormally expressed in hepatocellular carcinoma (HCC) and may serve as a potential molecular biomarker to ...evaluate the prognosis of hepatocellular carcinoma. Therefore, we accomplished a meta-analysis built on current studies to assess the prognostic value of lncRNAs in hepatocellular carcinoma.
Methods:
The PubMed database was carefully searched to collect all eligible studies until February 20, 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of the overall survival, relapse-free survival, and progression-free survival were calculated to evaluate the prognostic significance of lncRNAs expression in hepatocellular carcinoma using Stata12.0 software. Heterogeneity, sensitivity analysis, and publication bias were also evaluated.
Results:
The results showed that the expression level of lncRNAs was significantly correlated with clinical outcomes. Abnormally expressed lncRNAs predicted poor overall survival (HR=2.19, 95% CI: 1.99-2.42, P<0.001; I2=44.7%, P=0.005), relapse-free survival (HR=2.68, 95% CI: 1.74-4.14, P<0.001; I2=0.0%, P=0.763) and progression-free survival of hepatocellular carcinoma patients (HR=2.44, 95% CI: 1.53-3.89, P<0.001; I2=0.0%, P=0.336). Statistical significance was also noted in subgroup meta-analyses that were stratified by follow-up time, cutoff value, and quality score. Moreover, the pooled results indicated that lncRNAs expression was significantly associated with tumor size (HR=1.48, 95% CI: 1.24-1.79), tumor number (HR=1.34, 95% CI: 1.08-1.66), and tumor node metastasis stage (HR=2.10, 95% CI: 1.48-2.99), but not liver cirrhosis and tumor differentiation (P>0.05).
Conclusions:
This meta-analysis indicates that lncRNAs are strongly associated with prognosis in hepatocellular carcinoma and may serve as a promising indicator for prognostic evaluation of patients with hepatocellular carcinoma. But larger clinical studies are needed to verify its feasibility.
N-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA; 22:6n-3), has clinical significance in the prevention and reversal of nonalcoholic steatohepatitis (NASH). However, the precious ...mechanism underlying remains unclear. The inflammasome, a multiprotein complex formed by NOD-like receptor (NLR) family members, has been recently shown to be activated in NASH and promote the cleavage of the pro-inflammatory cytokines to their maturation forms.
HepG2 cells were exposed to different dose of PA for 24 h with or without the preincubation of 50 μM DHA for another 24 h and then lipid deposition was assessed with Oil red O staining and intracellular triglyceride (TG) determination. Secretory levels of inflammatory cytokines and Caspase-1 activity were determined by ELISA assays. Gene expression and protein levels were determined by quantitative RCR and western blotting, respectively.
Palmitate (PA) dose-dependently increased lipid accumulation, TG content and induced the secretion of interleukin-1β (IL-1β), IL-18, TNF-α and MCP-1 from HepG2 cells. Preincubation with DHA significantly alleviated PA-induced lipid accumulation and inflammatory agents. DHA was also found to attenuate PA-induced NOD-like receptor protein 4 (NLRC4) mRNA expression. Furthermore, PA induced caspase-1 activation in a dose-dependent manner, resulting in exacerbating of procaspase-1 and pro-IL-1β processing. Knockdown of NLRC4 partially abrogated PA-induced caspase-1 activation and IL-1β maturation and completely abolished these events in the presence of DHA.
Our findings indicate DHA attenuates PA-induced lipid accumulation and inflammation through suppressing NLRC4 inflammasome activation, caspase-1 activation and IL-1β cleavage.
A convenient and environmentally friendly method was developed for extraction and enrich of Sudan I from tomato sauce and chilli products. The method is based on an ultrasound-assisted dispersive ...liquid-liquid microextraction with solidification of floating organic drop (UADLLME-SFO) after a preliminary QuEChERS procedure, which was followed by high performance liquid chromatography with photodiode array detection (HPLC-PAD). The several parameters involved in the UADLLME-SFO step was optimized. The optimal variables obtained were 30 µL of 1-dodecanol as the extraction solvent, 1.0 mL of acetone as disperse solvent, ultrasonic irritation for 15 min, and no salt addition. Under the optimum conditions, the limit of detection for Sudan I was as low as 1.5 µg kg−1. The recoveries obtained was between 79% and 92% (RSD, 4.8% – 7.1%, n = 7). The proposed method was successfully applied to the determination of Sudan I in four kinds of real samples.
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